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Robustification of RosettaAntibody and Rosetta SnugDock

In recent years, the observed antibody sequence space has grown exponentially due to advances in high-throughput sequencing of immune receptors. The rise in sequences has not been mirrored by a rise in structures, as experimental structure determination techniques have remained low-throughput. Compu...

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Autores principales: Jeliazkov, Jeliazko R., Frick, Rahel, Zhou, Jing, Gray, Jeffrey J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993800/
https://www.ncbi.nlm.nih.gov/pubmed/33764990
http://dx.doi.org/10.1371/journal.pone.0234282
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author Jeliazkov, Jeliazko R.
Frick, Rahel
Zhou, Jing
Gray, Jeffrey J.
author_facet Jeliazkov, Jeliazko R.
Frick, Rahel
Zhou, Jing
Gray, Jeffrey J.
author_sort Jeliazkov, Jeliazko R.
collection PubMed
description In recent years, the observed antibody sequence space has grown exponentially due to advances in high-throughput sequencing of immune receptors. The rise in sequences has not been mirrored by a rise in structures, as experimental structure determination techniques have remained low-throughput. Computational modeling, however, has the potential to close the sequence–structure gap. To achieve this goal, computational methods must be robust, fast, easy to use, and accurate. Here we report on the latest advances made in RosettaAntibody and Rosetta SnugDock—methods for antibody structure prediction and antibody–antigen docking. We simplified the user interface, expanded and automated the template database, generalized the kinematics of antibody–antigen docking (which enabled modeling of single-domain antibodies) and incorporated new loop modeling techniques. To evaluate the effects of our updates on modeling accuracy, we developed rigorous tests under a new scientific benchmarking framework within Rosetta. Benchmarking revealed that more structurally similar templates could be identified in the updated database and that SnugDock broadened its applicability without losing accuracy. However, there are further advances to be made, including increasing the accuracy and speed of CDR-H3 loop modeling, before computational approaches can accurately model any antibody.
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spelling pubmed-79938002021-04-05 Robustification of RosettaAntibody and Rosetta SnugDock Jeliazkov, Jeliazko R. Frick, Rahel Zhou, Jing Gray, Jeffrey J. PLoS One Research Article In recent years, the observed antibody sequence space has grown exponentially due to advances in high-throughput sequencing of immune receptors. The rise in sequences has not been mirrored by a rise in structures, as experimental structure determination techniques have remained low-throughput. Computational modeling, however, has the potential to close the sequence–structure gap. To achieve this goal, computational methods must be robust, fast, easy to use, and accurate. Here we report on the latest advances made in RosettaAntibody and Rosetta SnugDock—methods for antibody structure prediction and antibody–antigen docking. We simplified the user interface, expanded and automated the template database, generalized the kinematics of antibody–antigen docking (which enabled modeling of single-domain antibodies) and incorporated new loop modeling techniques. To evaluate the effects of our updates on modeling accuracy, we developed rigorous tests under a new scientific benchmarking framework within Rosetta. Benchmarking revealed that more structurally similar templates could be identified in the updated database and that SnugDock broadened its applicability without losing accuracy. However, there are further advances to be made, including increasing the accuracy and speed of CDR-H3 loop modeling, before computational approaches can accurately model any antibody. Public Library of Science 2021-03-25 /pmc/articles/PMC7993800/ /pubmed/33764990 http://dx.doi.org/10.1371/journal.pone.0234282 Text en © 2021 Jeliazkov et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jeliazkov, Jeliazko R.
Frick, Rahel
Zhou, Jing
Gray, Jeffrey J.
Robustification of RosettaAntibody and Rosetta SnugDock
title Robustification of RosettaAntibody and Rosetta SnugDock
title_full Robustification of RosettaAntibody and Rosetta SnugDock
title_fullStr Robustification of RosettaAntibody and Rosetta SnugDock
title_full_unstemmed Robustification of RosettaAntibody and Rosetta SnugDock
title_short Robustification of RosettaAntibody and Rosetta SnugDock
title_sort robustification of rosettaantibody and rosetta snugdock
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993800/
https://www.ncbi.nlm.nih.gov/pubmed/33764990
http://dx.doi.org/10.1371/journal.pone.0234282
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